GMP Standard AI Control System Dispensing Hot Cell with Ultraviolet Ozone

The dispensing hot cell (or vialling hot cell) in a radiopharmaceutical production line is a critical aspect in the production process, located after the synthesis step. Its core task is to accurately dispense the synthesized and purified high-activity bulk radiopharmaceutical solution into multiple individual dose containers (such as injection vials or syringes) under aseptic conditions for patient use.

While sharing many common features with synthesis hot cells (such as radiation shielding, negative pressure, and HEPA filtration), the dispensing hot cell places greater emphasis on precision, sterility, speed, and reducing operator radiation exposure. Its main characteristics are as follows:

• Targeted Shielding: The dispensed nuclides are typically purified beta-plus (β+) or gamma (γ) emitters (e.g., F-18, Tc-99m). The shielding design is optimized for the specific energy of these nuclides.
• Front Shielding: Because operators need to work in front of the window for extended periods, the thickness of the front lead glass and lead bricks must ensure extremely low surface dose rates.
• "L"-Shaped Shield Blocks: Many dispensing hot cells are equipped with movable lead or tungsten bricks inside to surround vials or syringes during the dispensing process, further reducing radiation dose to the operator.

This is one of the most significant differences between dispensing and synthesis hot cells.Its internal environment requirements are extremely stringent.

• Grade A Clean Environment (ISO Class 5): The interior of the dispensing hot cell is typically equipped with a Laminar Airflow Hood or the entire internal space maintains Grade A air supply, ensuring the core dispensing operation area is in the cleanest state to prevent microbial and particulate contamination of the product.
• Surface Materials: Interior walls use high-grade stainless steel (e.g., 316L), which is smooth, seamless, corrosion-resistant, and can withstand frequent wiping with potent disinfectants (e.g., ethanol, hydrogen peroxide).
• Pass-Through Transfer: Many designs employ a Rapid Transfer Port (RTP) system. Product containers (e.g., vials) are secured in a dedicated shielded container, which couples with an interface on the hot cell wall to form a closed channel for transferring products in and out, minimizing the risk of external contamination.

The dispensing process is almost entirely automated to ensure dosage accuracy and operator safety.

• Precision Dispensing System: The core consists of high-precision piston pumps or syringe pumps, controlled by software, capable of dispensing specific volumes of liquid with extremely high accuracy (microliter level).
• Integrated Measurement: The system integrates a Radioisotope Dose Calibrator. The total activity of the bulk solution is measured before dispensing. During dispensing, the software automatically calculates the volume required for each vial to ensure each final product contains the preset radioactive activity (e.g., millicuries mCi or Megabecquerels MBq).
• Multi-Tasking Capability: Modern dispensing systems can automatically dispense into dozens or even hundreds of vials consecutively, including functions like capping, crimping, and labeling, without requiring manual intervention throughout the process.
• Syringe Dispensing Function: Many dispensing hot cells are also equipped with modules for direct dispensing into syringes for producing ready-to-use injections.

• Intuitive Software Interface: Operators set dispensing parameters (target activity, volume, number of vials, etc.) via a touchscreen interface. The entire process is visualized, and all data is recorded to meet GMP traceability requirements.
• Ease of Decontamination: The design simplifies cleaning procedures. The internal equipment layout is tidy, with piping minimized as much as possible, leaving ample space for routine cleaning and decontamination.
• Ergonomics: The height and viewing angle are designed to allow operators to comfortably observe the dispensing process. The range of the manipulators (if equipped) covers the main work areas.

• Process Monitoring: Cameras allow operators to closely monitor key steps such as the position of the dispensing needle, liquid level height, and stopper crimping.
• Data Integrity: The system automatically records all critical data for each dispensing batch, including: dispensing time, bulk solution activity, theoretical/actual activity per vial, operator ID, product batch number, etc. This data is crucial for drug release and quality traceability.

The dispensing hot cell is the final checkpoint for radiopharmaceuticals from production to clinical application. It no longer performs complex chemical reactions but acts as a high-speed, high-precision, ultra-clean radioactive dispensing robot. All its designs revolve around three ultimate goals:

1. Ensure Patient Safety: Guarantee that each dose is sterile, apyrogenic, and absolutely accurate.
2. Protect Operators: Minimize operator radiation exposure through optimal shielding and full automation.
3. Meet Regulatory Requirements: Fully comply with all GMP regulations for the production of sterile pharmaceuticals and data integrity.